TRA for Preventing Symptomatic Urinary Tract Infection Among High-risk Elderly Residing in Nursing Homes

Phase 2

Completed

• Conditions: Urinary Tract Infections
• Interventions: Drug: Concentrated herbal extract granules TRA; Drug: Placebo

• Registration Number: NCT04272437
• Lead Sponsor: Changhua Christian Hospital

Brief Summary

Urinary tract infection (UTI) is one of the most common infection in nursing home residents, and symptomatic UTI in the nursing home setting is the most frequent reason for hospitalization and antimicrobial therapy in Taiwan. Increasing antimicrobial resistance has stimulated interest in non-antibiotic prophylaxis of UTI. The primary aim of this study is to test the efficacy of standardized concentrated herbal extract granules TRA in the reduction of the incidence of symptomatic UTI and associated hospitalization in high-risk nursing home residents. These aims were accomplished by conducting a double-blind randomized placebo-controlled efficacy trial of TRA daily versus placebo granules in a cohort of Changhua County nursing home residents in Taiwan.

A total of 164 nursing home residents at high risk for UTI were be enrolled. A permuted block design with a block size of 6 were conducted. And a Stratification by nursing home accounted for potentially different standards of care. Subjects will be randomly assigned to receive either TRA (10 g) or the placebo two times per day for 42 consecutive days. All subjects in both groups will also continuously receive their daily medication without any dose or medicine change. Urinalysis was evaluated before and after administration. Independent statisticians performed the data analysis at the end of the trial.

Detailed Description

The standardized concentrated herbal extract granules TRA were the combination of "Tokoro Combination(Pi-Hsieh-Fen-Ching-Yin Extract Granules)" and "Rehmannia and Akebia Formula (Dao Chi San Extract Powder)". "Tokoro Combination" and "Rehmannia and Akebia Formula" in each one batch number were used, manufactured by Chuang Song Zong Pharmaceutical Co., Ltd., a famous GMP manufacturer of concentrated herbal extract granules in agreement with international standards. The TRA was prepared in small granules, including concentrated herbal extract granules of "Tokoro Combination"(50%) and "Rehmannia and Akebia Formula" (50%). Both medicines have already been approved by the Ministry of Health and Welfare in Taiwan as ethical drugs. TRA granules were packed in oblique glassine packages. The placebo was also prepared as granules by Chuang Song Zong Pharmaceutical Co., Ltd., and the packaging of the placebo was identical to that of TRA. The chemical composition of TRA was analyzed and profiled by using a high performance liquid chromatography (HPLC). The major components were diosgenin, yamogenin, betulin, oleanolic acid, hederagenin, akeboside, β-sitosterol, stigmasterol, inositol, catalpol, glycyrrhizin, etc.

Study Timeline

• Study Start: 2017-06-15
• Primary Completion: 2018-12-31
• Study Completion: 2019-03-03
• Status Verified: 2020-02
• Study First Submitted: 2020-02-10
• Study First Submitted QC: 2020-02-13
• Last Update Submitted: 2020-02-13
• Study First Posted: 2020-02-17
• Last Update Posted: 2020-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

1. Nursing home residents;

2. 65 years or older; and

3. High UTI risk

   • Catheterization (>1 m/o),
   • Diabetes mellitus, or
   • At least one UTI in the preceding year.

Exclusion Criteria

1. Not expected to be in the nursing home for at least one month (i.e. pending discharge, terminal life expectancy < 1 month);
2. On chronic suppressive antibiotic or anti-infective therapy
3. On dialysis for end stage renal disease; or
4. previous ADR to herbals.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TRA group	Concentrated herbal extract granules TRA	"Tokoro Combination" and "Rehmannia and Akebia Formula" (TRA) in each one batch number were manufactured by Chuang Song Zong Pharmaceutical Co., Ltd., a famous manufacturer of concentrated herbal extract granules in agreement with the standards of good manufacturing practices (GMP) in Kaohsiung City, Taiwan. TRA contains "Tokoro Combination" and "Rehmannia and Akebia Formula" "Tokoro Combination" and "Rehmannia and Akebia Formula" consists of Dioscorea Hypoglaucae Rhizoma, Acori Graminei Rhizoma, Linderae Radix, Alpiniae Oxyphyllae Fructus, Poria, Rehmanniae Radix, Akebiae Caulis, Lophatheri Hebra, and Glycyrrhizae Radix at a 2:2:2:2:1:1.3:1.3:1.3:2.5 ratio.
placebo group	Placebo	The placebo was also prepared as granules by Chung Song Zong Pharmaceutical Co., Ltd., and the packaging of the placebo was identical to that of TRA.

Primary Outcome Measures

Name	Time	Method
Number of Episodes of Symptomatic UTI During Administration	42 days	Nursing home medical record and National Health Insurance(NHI) IC cards checking were both performed every week for the symptomatic UIT diagnosis and hospitalization recording. Suspected UTI episodes that were recorded in nursing home medical record were reviewed by chart review, symptoms, signs, and laboratory data were recorded, two investigators determined if the definition of symptomatic UTI was met.

Secondary Outcome Measures

Name	Time	Method
Number of Episodes of Symptomatic UTI Onset From First Administration Till 180 Days	180 days.	Nursing home medical record and National Health Insurance(NHI) IC cards checking were both performed every week for the symptomatic UIT diagnosis and hospitalization recording. Suspected UTI episodes that were recorded in nursing home medical record were reviewed by chart review, symptoms, signs, and laboratory data were recorded, two investigators determined if the definition of symptomatic UTI was met.
Accumulated Rate of Symptomatic UTI During Administration	42 days.	Nursing home medical record and National Health Insurance(NHI) IC cards checking were both performed every week for the symptomatic UIT diagnosis and hospitalization recording. Suspected UTI episodes that were recorded in nursing home medical record were reviewed by chart review, symptoms, signs, and laboratory data were recorded, two investigators determined if the definition of symptomatic UTI was met.
Accumulated Rate of Symptomatic UTI Onset From First Administration Till 180 Days	180 days.	Nursing home medical record and National Health Insurance(NHI) IC cards checking were both performed every week for the symptomatic UIT diagnosis and hospitalization recording. Suspected UTI episodes that were recorded in nursing home medical record were reviewed by chart review, symptoms, signs, and laboratory data were recorded, two investigators determined if the definition of symptomatic UTI was met.
The Change of Urinalysis From Baseline to 42 Days	42 days	Sterile urine specimen collection from a foley catheter or clean catch midstream urine for urinalysis were obtained from baseline to 6 weeks for each participant for study purposes.; Changes in urine species were texted by using chemical strip and urine sediment method in the Department of Laboratory Medicine at ChungHua Christrian Hospital. The items for urinalysis were as following: specific gravity, pH value, protein, nitrite, WBC esterase, RBC( in high-power field), RBC( in high-power field), squamous epithelial cell( in high-power field), bacteria( in high-power field), etc.
Number of Deaths Onset From First Administration Till 180 Days	180 days	All-cause deaths were recorded.

Trial Locations

Locations (1)

Dept. of Traditional Chinese Medicine, Changhua Christian Hospital; 🇨🇳 Changhua city, Taiwan